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1.
Yonsei Med J ; 65(7): 389-396, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38910301

RESUMO

PURPOSE: This study was conducted to develop a convolutional neural network (CNN) algorithm that can diagnose cervical foraminal stenosis using oblique radiographs and evaluate its accuracy. MATERIALS AND METHODS: A total of 997 patients who underwent cervical MRI and cervical oblique radiographs within a 3-month interval were included. Oblique radiographs were labeled as "foraminal stenosis" or "no foraminal stenosis" according to whether foraminal stenosis was present in the C2-T1 levels based on MRI evaluation as ground truth. The CNN model involved data augmentation, image preprocessing, and transfer learning using DenseNet161. Visualization of the location of the CNN model was performed using gradient-weight class activation mapping (Grad-CAM). RESULTS: The area under the curve (AUC) of the receiver operating characteristic curve based on DenseNet161 was 0.889 (95% confidence interval, 0.851-0.927). The F1 score, accuracy, precision, and recall were 88.5%, 84.6%, 88.1%, and 88.5%, respectively. The accuracy of the proposed CNN model was significantly higher than that of two orthopedic surgeons (64.0%, p<0.001; 58.0%, p<0.001). Grad-CAM analysis demonstrated that the CNN model most frequently focused on the foramen location for the determination of foraminal stenosis, although disc space was also frequently taken into consideration. CONCLUSION: A CNN algorithm that can detect neural foraminal stenosis in cervical oblique radiographs was developed. The AUC, F1 score, and accuracy were 0.889, 88.5%, and 84.6%, respectively. With the current CNN model, cervical oblique radiography could be a more effective screening tool for neural foraminal stenosis.


Assuntos
Algoritmos , Vértebras Cervicais , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Estenose Espinal , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estenose Espinal/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Adulto , Idoso , Curva ROC , Radiografia/métodos
2.
Nat Commun ; 13(1): 2572, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35546148

RESUMO

Recent development of the chemical inhibitors specific to oncogenic KRAS (Kirsten Rat Sarcoma 2 Viral Oncogene Homolog) mutants revives much interest to control KRAS-driven cancers. Here, we report that AIMP2-DX2, a variant of the tumor suppressor AIMP2 (aminoacyl-tRNA synthetase-interacting multi-functional protein 2), acts as a cancer-specific regulator of KRAS stability, augmenting KRAS-driven tumorigenesis. AIMP2-DX2 specifically binds to the hypervariable region and G-domain of KRAS in the cytosol prior to farnesylation. Then, AIMP2-DX2 competitively blocks the access of Smurf2 (SMAD Ubiquitination Regulatory Factor 2) to KRAS, thus preventing ubiquitin-mediated degradation. Moreover, AIMP2-DX2 levels are positively correlated with KRAS levels in colon and lung cancer cell lines and tissues. We also identified a small molecule that specifically bound to the KRAS-binding region of AIMP2-DX2 and inhibited the interaction between these two factors. Treatment with this compound reduces the cellular levels of KRAS, leading to the suppression of KRAS-dependent cancer cell growth in vitro and in vivo. These results suggest the interface of AIMP2-DX2 and KRAS as a route to control KRAS-driven cancers.


Assuntos
Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Transformação Celular Neoplásica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
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